Asimadoline for the Treatment of Post-Operative Ileus

A Randomized, Double-Blind, Placebo-Controlled Study Evaluating Asimadoline on the Duration of POI in Subjects Undergoing Laparoscopic/Hand-Assisted Lap Segmental Colonic Resection Secondary to Colon Cancer, Polypectomy or Diverticulitis

The purpose of this study is to evaluate the safety and efficacy of asimadoline in patients who have undergone a laparoscopic segmental colectomy and determine whether it reduces the time to recovery of bowel function compared to placebo.

Study Overview

• Status: Terminated
• Conditions: Post-Operative Ileus
• Intervention / Treatment: Drug: Placebo; Drug: Asimadoline

Detailed Description

This randomized, double-blind, placebo-controlled study was designed to evaluate the efficacy and tolerability of two dose levels of asimadoline on the duration of post-operative ileus in subjects undergoing laparoscopic or hand-assisted laparoscopic colon resections. Subjects meeting entry criteria were randomized in a 1:1:1 ratio to receive either asimadoline 1.0 mg, asimadoline 3.0 mg or a placebo. One hundred and fourteen subjects were planned, and in the event that a subject was converted from a laparoscopic surgery to an open surgery (laparotomy), that subject would be discontinued from the trial and followed for safety only. The protocol allowed subjects converted to open procedures to be replaced. The first dose was administered approximately 90 minutes pre-operatively, and subsequent dosing was b.i.d. for up to 10 post-operative doses. Subjects were dosed with study drug only while in the hospital. After discharge, they were followed for an additional 28 days. Total study duration for each patient was approximately 5 to 6 weeks.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Burlington, Massachusetts, United States, 01805
      • Lahey Clinic
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University
  • Ohio
    • Cleveland, Ohio, United States, 44106-5047
      • University Hospitals of Cleveland
  • Pennsylvania
    • Wynnewood, Pennsylvania, United States, 19096
      • Marks Colorectal Surgical Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females aged 18-80
• Must be scheduled to undergo a laparoscopic/hand-assisted laparoscopic segmental colectomy
• Must sign an ICF
• Females of childbearing potential must have a negative pregnancy test at screening

Exclusion Criteria:

• Subjects with evidence of a biochemical or structural abnormality of the GI tract or other co-morbid illness that may impact the ability to interpret the safety and efficacy data
• Pregnant or breastfeeding females
• Use of investigational drugs in previous 30 days
• Refusal to discontinue prohibited concomitant medications
• Chronic use of prescription narcotics over the previous 6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Placebo was provided in coated tablets identical in appearance to asimadoline tablets. Subjects were given 3 tablets of placebo 90 minutes prior to their operation and then 3 placebo tablets b.i.d. for up to 10 post-operative doses.
ACTIVE_COMPARATOR: Asimadoline 1.0 mg; Asimadoline 1.0 mg b.i.d.	Drug: Asimadoline; Asimadoline was provided in coated tablets of 1.0 mg strength. Subjects were given 3 tablets of study drug 90 minutes prior to their operation and then 3 tablets b.i.d. for up to 10 post-operative doses. Subjects randomized to receive 3.0 mg of asimadoline received three 1.0 mg asimadoline tablets at each scheduled dose, while those randomized to receive 1.0 mg of asimadoline received two placebo tablets and one 1.0 mg asimadoline tablet at each scheduled dose.; Other Names: EMD 61 753; EMR 63 320
ACTIVE_COMPARATOR: Asimadoline 3.0 mg; Asimadoline 3.0 mg b.i.d.	Drug: Asimadoline; Asimadoline was provided in coated tablets of 1.0 mg strength. Subjects were given 3 tablets of study drug 90 minutes prior to their operation and then 3 tablets b.i.d. for up to 10 post-operative doses. Subjects randomized to receive 3.0 mg of asimadoline received three 1.0 mg asimadoline tablets at each scheduled dose, while those randomized to receive 1.0 mg of asimadoline received two placebo tablets and one 1.0 mg asimadoline tablet at each scheduled dose.; Other Names: EMD 61 753; EMR 63 320

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Return of Upper and Lower GI Function	The time to first bowel movement or the time to tolerating solid food, whichever occurs later.	Daily for 38 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Tolerating Solid Food	Time to tolerating solid food (toleration is defined as the absence of nausea or vomiting) within 4 hours of ingesting a meal	4 hours of ingesting a meal
Time to First Passage of Flatus		Daily for 38 days
Time to First Bowel Movement		Daily for 38 days
Time to Writing of Hospital Discharge Order		Daily for 38 days
Nausea Score		Daily for 38 days
Vomiting Score		Daily for 38 days
Pain Score		Daily for 38 days
Nasogastric Tube Re-insertion	Proportion of subjects with nasogastric tube re-insertion	Daily for 38 days
Post-operative Analgesic Use		Daily for 38 days
Adverse Events	Adverse events grouped by body system	Daily for 38 days
Laboratory Values	Changes in laboratory values.	Daily for 38 days

Collaborators and Investigators

• Sponsor: Tioga Pharmaceuticals
• Collaborators: RTI Health Solutions
• Investigators: Study Chair: Allen Mangel, MD, PhD, CMO

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (ACTUAL): February 1, 2008
• Study Completion (ACTUAL): February 1, 2008

Study Registration Dates

• First Submitted: February 27, 2007
• First Submitted That Met QC Criteria: March 1, 2007
• First Posted (ESTIMATE): March 5, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): January 6, 2012
• Last Update Submitted That Met QC Criteria: November 30, 2011
• Last Verified: November 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Obstruction; Ileus
• Other Study ID Numbers: ASMP2004